Current Literature In Clinical Science

Are We Winning the Battle But Losing the War? Sequelae of Surviving Epilepsy

Childhood-Onset Epilepsy Five Decades Later. A Prospective Population-Based Cohort Study. Sillanpää M, Anttinen A, Rinne JO, Joutsa J, Sonninen P, Erkinjuntti M, Hermann B, Karrasch M, Saarinen M, Tiita P, Shinnar S. Epilepsia 2015;56:1774–1783. doi:10.1111/epi.13187.

OBJECTIVE: To study the impact of childhood-onset epilepsy on a variety of outcomes across the life span. METHODS: A population-based cohort of 245 subjects with childhood-onset epilepsy was assessed for outcomes at 45 years. In addition, 51 of 78 surviving subjects with uncomplicated epilepsy and 52 of 99 originally matched controls participated in a detailed evaluation including electroencephalography (EEG), imaging, and laboratory studies at 50 years. RESULTS: Of 179 surviving subjects, 61% were in terminal 10-year remission and 43% in remission off medications. At 45 years, 95% of the idiopathic group, 72% of the cryptogenic group, and 47% of the remote symptomatic group were in terminal remission (p < 0.001). Abnormal neurologic signs were significantly more common in subjects with uncomplicated epilepsy than in controls. Mortality during period 1992–2012 was higher in subjects than in controls (9% vs. 1%, p = 0.02). The rate of 3T MRI abnormalities was higher in subjects than in controls (risk ratio [RR] 2.0; 1.3–3.1) specifically including findings considered markers of cerebrovascular disease (RR 2.5; 1.04–5.9). Even subjects with idiopathic epilepsy had higher rates of imaging abnormalities than controls (73% vs. 34%, p = 0.002). SIGNIFICANCE: Long-term seizure outcomes are excellent and a function of etiology. The presence of imaging abnormalities suggestive of vascular disease may put these subjects at higher risk for clinically evident stroke and cognitive changes as they age.

Commentary The initial diagnosis of epilepsy in childhood, whether from a “benign” or devastating etiology, is traumatic for patients and their families. The initial visits with their healthcare provider are filled with questions about treatment, etiology, and most important, the expectations for the future. While we are fortunate in pediatric epilepsy to have many age-limited syndromes or other cryptogenic causes of seizures, which ultimately remit with few aftereffects, many epilepsies can result in significant and long-lasting cognitive, social, and comorbid health problems. These long-lasting sequelae are not restricted to those with intractable epilepsy, as even the most “benign” syndromes, such as benign rolandic epilepsy, may cause cognitive and behavioral problems long after the epilepsy has remitted (1). For many, the sequelae of epilepsy may not only be secondary to the primary disease but also to the treatments used in the course of their care. In many ways, pediatric epilepsy draws parallels to childhood cancer in this sense. Our treatments have continued to improve, and many children will grow up to lead seizure-free lives thanks to advancements in medical therapy and surgical options. However, whether their lives will be as healthy as those without a history of epilepsy Epilepsy Currents, Vol. 16, No. 3 (May/June) 2016 pp. 139–140 © American Epilepsy Society

is still poorly understood. Unlike our colleagues in oncology, we have too often failed to look beyond seizure remission when considering the consequences of an epilepsy diagnosis and treatment. Many studies of long-term outcomes present data spanning only a few years. While some longer retrospective studies exceed 20 years of follow-up, the focus often remains on seizure remission more so than comorbid health problems (2). We know psychosocial outcome is often poorer in patients with epilepsy compared with the general population, with lower rates of marriage, learning achievement, and employment in those with a history of seizures (3). The adverse psychosocial impact of epilepsy is most pronounced in childhood-onset disease and is influenced by the continued need for treatment, regardless of seizure-free status (4, 5). The impact that the diagnosis and treatment of childhood-onset epilepsy has on other aspects of health in long-term “survivors” is not as clear. If we hope to improve our care of epilepsy, not just for achievement of seizure freedom but also for management of associated comorbidities, we must better understand the long-term consequences of the disease. Sillanpää and colleagues continue pioneering work investigating the long-term outcomes of pediatric epilepsy in their most recent analysis of the Turku Adult Childhood Onset Epilepsy study, a prospective population-based cohort with up to 50 years of follow-up data. The population studied represents a collection of 245 patients with childhood-onset epilepsy who were evaluated and treated by a single neurolo-

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Long-Term Health Outcomes in Epilepsy

gist. Twenty-seven percent of the patients died over the course of the study, many as a direct result of their epilepsy, underscoring the severity of this disease. Still, 74% of the patients remained in the study providing insight into both seizure remission and associated health outcomes. As one would expect, the results showed that long-term seizure freedom is a very attainable goal for all patients with 61% in terminal 10-year seizure remission by 45 years and 43% off medications. Those with symptomatic etiologies were less likely to remit compared with idiopathic/cryptogenic causes, though 47% still attained remission, albeit more often on medication. Patients with cryptogenic etiology approached the remission rates of those with idiopathic etiology by 50 years, a finding not present in analysis of shorter follow-up durations, thus giving hope to adults still searching for seizure control. At the same time, some patients who entered 10-year remission had seizure relapse—suggesting we still cannot completely define resolved epilepsy. While the long-term seizure remission data are of great value in counseling patients, the authors complete an additional analysis highlighting other comorbid outcomes, which is a strength of this study. Comparing a 50-year cohort of uncomplicated epilepsy (i.e., those without other neurologic impairments at onset) with matched controls without epilepsy, the authors found that abnormal neurologic signs and mortality were more common in those with a history of epilepsy. Many of these patients died from vascular disease and cancer—not their seizures. Even more striking, the authors found imaging markers of cerebrovascular disease were significantly more common in patients with epilepsy, unrelated to typical risk factors (i.e., smoking, body mass index, alcohol use, or cholesterol) and irrespective of epilepsy etiology. It is unclear whether these imaging findings predate the diagnosis of epilepsy, as modern imaging techniques were not available when the cohort presented, though the majority of imaging findings were not felt to be the cause of seizures. It is also unknown whether

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the imaging findings will ultimately be clinically significant— but it suggests that there are additional long-term burdens of epilepsy of which we are only now becoming aware. Might these findings contribute to the psychosocial and cognitive declines seen in patients with epilepsy? Since even seizurefree patients continue to suffer psychosocial and cognitive deficits compared with healthy controls, could these findings offer another malleable contributor to epilepsy outcome that we can alter early in the course of the disease? Understanding long-term sequelae in epilepsy survivors is of great value to improving care and may open doors to novel approaches altering the course of the disease. Further longterm studies of comorbid health conditions in epilepsy survivors—defining the source of such conditions, be it the seizures themselves, the etiology of epilepsy, or our treatments—will help shape the future of epilepsy management. While the ultimate goal remains a cure, we must begin to recognize the potential sequelae a cure will leave behind, before it is too late to avoid unintended adverse outcomes. by M. Scott Perry, MD References 1. Vannest J, Tenney JR, Gelineau-Morel R, Maloney T, Glauser TA. Cognitive and behavioral outcomes in benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 2015;45:85–91. 2. Kurtz Z, Tookey P, Ross E. Epilepsy in young people: 23 year follow up of the British national child development study. BMJ 1998;316:339– 342. 3. Shackleton DP, Kasteleijn-Nolst Trenité DG, de Craen AJ, Vandenbroucke JP, Westendorp RG. Living with epilepsy: Long-term prognosis and psychosocial outcomes. Neurology 2003;61:64–70. 4. Sillanpää M, Jalava M, Kaleva O, Shinnar S. Long-term prognosis of seizures with onset in childhood. N Engl J Med 1998;338:1715–1722. 5. Sillanpää M, Haataja L, Shinnar S. Perceived impact of childhood-onset epilepsy on quality of life as an adult. Epilepsia 2004;45:971–977.

Are We Winning the Battle But Losing the War? Sequelae of Surviving Epilepsy.

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